TUMOR NECROSIS FACTOR ALPHA SIGNALING IN BREAST CANCER

乳腺癌中的肿瘤坏死因子α信号传导

• 批准号: 2397407
• 负责人: Alakananda Basu
• 金额: $ 17.81万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-04 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2397407
• 关键词: antisense nucleic acid; apoptosis; biological signal transduction; breast neoplasms; cytokine receptors; enzyme activity; human genetic material tag; human tissue; isozymes; neoplasm /cancer genetics; neoplasm /cancer pharmacology; phosphoproteins; protein kinase C; receptor binding; receptor coupling; receptor expression; tissue /cell culture; tumor necrosis factor alpha; tumor suppressor genes

DESCRIPTION: Tumor necrosis factor-alpha (TNF) influences a wide variety of cellular functions, including cell growth, cell death and metastases. Although the action of TNF is mediated through its cell surface receptors, the intracellular events that link ligand binding to the cytotoxic action of TNF remain elusive. The overall objective of this grant application is to define the signaling mechanisms that regulate TNF-mediated cell killing. Signaling through TNF receptors (TNFR) is unique. They do not possess any intrinsic kinase activity. It is presumed that upon ligand binding TNFR activate and/or recruit other factors or kinases to convey its signal. The specific focus of this project is to define the functional significance of protein phosphorylation and dephosphorylation in TNF signaling. TNF inhibits the growth of breast cancer cells in vitro but little is known regarding the involvement of TNF in breast cancer pathogenesis. The protein kinase C signal transduction pathway appears to regulate TNF sensitivity in breast cancer cells. The specific aims of this application are to determine the contribution of PKC isozymes in TNF-mediated cell death, to study the regulation of TNFR function by kinases, to investigate their involvement on the down-stream signaling events of TNF and to determine the basis for TNF resistance in normal and malignant mammary cells.

描述：肿瘤坏死因子-α (TNF) 影响多种 细胞功能，包括细胞生长、细胞死亡和转移。 尽管 TNF 的作用是通过其细胞表面受体介导的， 将配体结合与细胞毒性作用联系起来的细胞内事件 TNF 仍然难以捉摸。 本次赠款申请的总体目标是 定义调节 TNF 介导的细胞杀伤的信号机制。 通过 TNF 受体 (TNFR) 发出的信号是独特的。 他们不拥有任何 内在激酶活性。 据推测，配体结合 TNFR 激活和/或招募其他因子或激酶来传递其信号。 这 该项目的具体重点是定义功能意义 TNF 信号传导中的蛋白质磷酸化和去磷酸化。 肿瘤坏死因子 在体外抑制乳腺癌细胞的生长，但人们知之甚少 关于 TNF 在乳腺癌发病机制中的作用。 蛋白质 激酶 C 信号转导途径似乎可以调节 TNF 敏感性 乳腺癌细胞。 该应用程序的具体目标是确定 PKC 同工酶在 TNF 介导的细胞死亡中的作用，以研究 激酶对 TNFR 功能的调节，以研究它们对 TNF的下游信号传导事件并确定TNF的基础 正常和恶性乳腺细胞的抵抗力。